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Cited by 233Pancreatic function and diabetesDiabetes and associated disordersEndoplasmic Reticulum Stress and Disease

IFN- gamma and tumor necrosis factor- alpha . Cytotoxicity to murine islets of Langerhans.

Campbell, I L, Iscaro, A, Harrison, L C·1988·The Journal of Immunology
DOI 10.4049/jimmunol.141.7.2325
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Abstract

We have previously reported that the cytokines IFN-gamma and TNF-alpha each upregulate the expression of class I MHC proteins and, in combination, induce the expression of class II MHC proteins on pancreatic islet cells. IFN-gamma and TNF-alpha are therefore implicated in the immunologic destruction of beta-cells in insulin-dependent diabetes mellitus. The objective of the present study was to define the effects of IFN-gamma and TNF-alpha on the function and viability of murine pancreatic islet beta-cells in vitro. Exposure of islets for 3 days to 200 U/ml of either IFN-gamma or TNF-alpha did not affect glucose-stimulated insulin release, but at higher concentrations (2000 U/ml) of either cytokine there was significant inhibition of glucose-stimulated insulin release. In combination, IFN-gamma and TNF-alpha each at 200 U/ml caused significant inhibition of glucose-stimulated insulin release; at 2000 U/ml glucose-stimulated insulin release was abolished. In time-course experiments, glucose-stimulated insulin release from islets exposed to IFN-gamma and TNF-alpha each at 1000 U/ml was significantly increased at 4-h (twofold increase compared with control islets), decreased back to control levels at 18 h, significantly inhibited by 24 h (threefold decrease compared with control islets), and completely abolished by 48 h. The progressive impairment of beta-cell function mediated by IFN-gamma plus TNF-alpha was associated with morphologic derangement of the islets that were almost totally disintegrated by day 6 of exposure to the cytokines. At day 6, insulin content of the islets was significantly reduced by exposure to TNF-alpha but not IFN-gamma. The combination of IFN-gamma and TNF-alpha resulted in a further dose-dependent depletion in insulin content compared with TNF-alpha alone. The synergistic functional and cytotoxic effects of IFN-gamma and TNF-alpha are consistent with a direct role for these cytokines in the destruction of beta-cells in insulin-dependent diabetes.

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  • The proinflammatory cytokines, such as IL-1β, IFN-γ, and TNF-α, inhibit glucose-stimulated insulin secretion and proliferation of beta-cells.

    “The proinflammatory cytokines, such as interleukin-1 beta (IL-1β), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α), inhibit glucose-stimulated insulin secretion and proliferation of beta-cells [40–42].”

    From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [40]

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Authors
Campbell, I. L., Iscaro, A., & Harrison, L. C.
Affiliations
The Royal Melbourne Hospital (AU)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
1988-10-01
Volume
141
Issue
7
Pages
2325-2329
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.141.7.2325
OpenAlex
W1565885233
Cited by
233
References
0
Citations by year
2022: 4 · 2021: 2 · 2019: 2 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 2
FWCI
20.00
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
interferon-gamma, TNF-α, pancreatic islets, beta-cell cytotoxicity, glucose-stimulated insulin secretion, type 1 diabetes, beta cell destruction, cytokine synergy, islet morphology, insulin content
MeSH terms
Animals, Cells, Cultured, Drug Combinations, Glucose, Insulin, Interferon-gamma, Islets of Langerhans, Kinetics, Tumor Necrosis Factor-alpha, Mice

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